CA2339325C - Implantable nuclear magnetic resonance spectrometer - Google Patents
Implantable nuclear magnetic resonance spectrometer Download PDFInfo
- Publication number
- CA2339325C CA2339325C CA002339325A CA2339325A CA2339325C CA 2339325 C CA2339325 C CA 2339325C CA 002339325 A CA002339325 A CA 002339325A CA 2339325 A CA2339325 A CA 2339325A CA 2339325 C CA2339325 C CA 2339325C
- Authority
- CA
- Canada
- Prior art keywords
- magnetic resonance
- nuclear magnetic
- fluid
- implantable
- catheter
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
- G01R33/30—Sample handling arrangements, e.g. sample cells, spinning mechanisms
- G01R33/302—Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/48—Other medical applications
- A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
- A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/28—Details of apparatus provided for in groups G01R33/44 - G01R33/64
- G01R33/30—Sample handling arrangements, e.g. sample cells, spinning mechanisms
- G01R33/307—Sample handling arrangements, e.g. sample cells, spinning mechanisms specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer
Landscapes
- Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pathology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Physics & Mathematics (AREA)
- Public Health (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Biophysics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- High Energy & Nuclear Physics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Radiology & Medical Imaging (AREA)
- Dispersion Chemistry (AREA)
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Measuring Volume Flow (AREA)
- Measuring And Recording Apparatus For Diagnosis (AREA)
- External Artificial Organs (AREA)
- Magnetic Treatment Devices (AREA)
Abstract
Implantable nuclear magnetic resonance spectrometer contained in a housing comprising a permanent magnet arrangement (1,2,3,4) for generating a static magnetic field of suitable intensity and homogeneity for analysing a sample of fluid flowing into a catheter (6) traversing the implant. The implant further comprises an arrangement of electronic circuits (8,9) responsible for the excitation and detection of the nuclear magnetic resonance signal and at least one coil (7) to expose the fluid sample to the excitation signal and to collect the returned nuclear magnetic resonance signal. The implant also comprises the necessary RF circuits and an antenna (10) for communicating by conventional telemetry with an inductively coupled reader.
Description
Implantable nuclear magnetic resonance spectrometer.
The present invention relates to a medical implant, more particularly to a medical implantable device comprising a magnetic nuclear resonance spectrometer arrangement capable of characterising and monitoring the local flow rate of a physiological fluid as well as its chemical composition.
Nuclear magnetic resonance is based on the following known principle. All atomic nuclei with an odd atomic mass or an odd atomic number (like hydrogen for example) possess an intrinsic nuclear magnetic momentum. Without entering the io details, one can consider that this momentum is generated by the rotation of the proton around the nucleus. When a NMR active nucleus is placed in a static magnetic field, this momentum can take two different orientations. The momentum may take either an orientation parallel to the magnetic field or an antiparallel orientation relative to the magnetic filed. Considering a population of hydrogen atoms immersed in the same static magnetic field, the number of atoms having a parallel orientation is slightly greater than the number of atoms having an anti-parallel orientation. This is due the fact that the parallel orientation is energetically more favourable. The passage from the parallel state to the anti parallel state occurs when the atoms absorb electromagnetic energy at a given frequency called the resonance frequency. This resonance frequency depends on the nucleus of the atom and on the intensity of the static magnetic field. A magnetic nuclear resonance apparatus works by analysing the signal emitted during the transition from the excited state (anti-parallel) to the state of equilibrium (parallel).
The nuclei are placed in a high intensity static magnetic field and then exited with an electromagnetic wave having a frequency corresponding to the resonance frequency. When the return to the equilibrium state occurs, a signal having the same frequency as the excitation signal (resonance) is generated and can be measured thanks to an antenna.
The present invention relates to a medical implant, more particularly to a medical implantable device comprising a magnetic nuclear resonance spectrometer arrangement capable of characterising and monitoring the local flow rate of a physiological fluid as well as its chemical composition.
Nuclear magnetic resonance is based on the following known principle. All atomic nuclei with an odd atomic mass or an odd atomic number (like hydrogen for example) possess an intrinsic nuclear magnetic momentum. Without entering the io details, one can consider that this momentum is generated by the rotation of the proton around the nucleus. When a NMR active nucleus is placed in a static magnetic field, this momentum can take two different orientations. The momentum may take either an orientation parallel to the magnetic field or an antiparallel orientation relative to the magnetic filed. Considering a population of hydrogen atoms immersed in the same static magnetic field, the number of atoms having a parallel orientation is slightly greater than the number of atoms having an anti-parallel orientation. This is due the fact that the parallel orientation is energetically more favourable. The passage from the parallel state to the anti parallel state occurs when the atoms absorb electromagnetic energy at a given frequency called the resonance frequency. This resonance frequency depends on the nucleus of the atom and on the intensity of the static magnetic field. A magnetic nuclear resonance apparatus works by analysing the signal emitted during the transition from the excited state (anti-parallel) to the state of equilibrium (parallel).
The nuclei are placed in a high intensity static magnetic field and then exited with an electromagnetic wave having a frequency corresponding to the resonance frequency. When the return to the equilibrium state occurs, a signal having the same frequency as the excitation signal (resonance) is generated and can be measured thanks to an antenna.
The resonance detection may occur either at the stage of excitation, by measuring the energy absorption by scanning a range of frequency or when the atoms return to the state of equilibrium. In the later, one measures the electromagnetic signal emitted by the magnetic momentum returning to their equilibrium position. If other atoms than hydrogen atoms are present in the solution to be characterised, the spin of their electrons will generate a magnetic field at the microscopic level. Thus the hydrogen atoms are submitted to the static magnetic field generated by the NMR device to which is superposed locally the magnetic field generated by the electrons. This will alter the resonance frequency io with a signature specific to the environment of the hydrogen atoms within the solution to characterise. Nuclear magnetic resonance spectroscopy is based on this principle and is mainly used for two different kind of applications, namely for biochemical analysis in laboratories and in magnetic resonance imaging spectroscopy. In laboratories, nuclear magnetic resonance spectroscopy is usually performed at very high magnetic field intensity (> 10 Tesla) to reveal the atomic structure of molecules. In contrast magnetic resonance imaging spectroscopy (MRIS) is performed with standard MRI equipment at lower filed intensity (around 1.5 Tesla) to reveal the composition of the tissues environment at molecular level.
It is also possible to gather information related to the flow of a liquid by 2o analysing the signal returning to the equilibrium state after a resonant excitation.
This signal has a decrease, which is characteristic when the liquid is static, and a faster decrease when the liquid is in movement. This is due to the fact that part of the excited atoms will leave the detection volume of the antenna. This technique also used in magnetic resonance imaging spectroscopy devices.
Chronic monitoring of specific chemical compounds in a body fluid as well as gathering information relative to the flow rate of a fluid within the human body is a key in many areas of medicine, this is particularly true for brain metabolites monitoring in trauma patient or for monitoring the flow rate of the cerebrospinal fluid in a shunted hydrocephalic patient. The known techniques for monitoring the concentration of specific chemical compounds in a physiological fluid are usually achieved invasively either by techniques that require taking samples of the fluid (dialysis,..) or by inserting probes in the targeted fluid/tissue (micro dialysis, blood gas analysis.) These techniques involve either a puncture for each sample to analyse or a catheter line to be left in place for the duration of the monitoring.
Furthermore, invasive catheter probes are mainly targeted to specific analytes such as 02, C02, glucose or lactose.
Other non-invasive techniques such as magnetic resonance imaging spectroscopy are rather expensive and do not permit a continuous monitoring.
Moreover, concerning the flow rate assessment, there are currently no known devices to perform these measures in situ.
The aim of the present invention is to remedy the aforesaid drawbacks.
This goal is achieved by an implantable nuclear magnetic resonance spectrometer having the characteristic recited in claim 1.
Yet another object of the invention is the use of said implantable nuclear resonance spectrometer in several medical applications.
In accordance with one aspect, there is provided an implantable nuclear magnetic resonance spectrometer for at least one of measuring the chemical composition of a fluid and measuring the flow rate of the fluid, the spectrometer comprising: a housing; a catheter transversing across the housing so that a fluid external to the housing may flow through the catheter within the housing; a permanent magnet disposed within the housing that generates an intense homogenous magnetic field in the vicinity of the catheter; an electronics circuit disposed within the housing for detecting and formatting a nuclear magnetic resonance excitation signal; and at least one excitation coil connected to the electronic circuit and being disposed about the catheter to expose the fluid within the catheter to the excitation signal and to collect the nuclear magnetic resonance excitation signal.
In accordance with a further aspect, there is provided an apparatus for at least one of measuring the chemical composition of a physiological fluid and for measuring the flow rate of the fluid, comprising: an implantable nuclear magnetic 3a resonance spectrometer having a catheter extending therethrough so that a fluid external to the spectrometer may flow through the catheter to be analyzed; and an external reader having means for communicating with the implantable spectrometer by telemetry.
In accordance with a further aspect, there is provided use of the implantable nuclear magnetic resonance spectrometer described herein for at least one of measuring the chemical composition of a physiological fluid and measuring the flow rate of the fluid.
In accordance with a further aspect, there is provided use of the apparatus described herein for at least one of measuring the chemical composition of a physiological fluid and measuring the flow rate of the fluid.
Further features and other objects and advantages of this invention will become clear from the following detailed description made with reference to the accompanying drawings illustrating in a schematic and non-limiting way one embodiment of the implantable nuclear magnetic resonance spectrometer.
Figure 1 is a schematic partially cross-sectional view of the implantable nuclear magnetic resonance spectrometer object of the present invention.
Referring to fig 1, there is shown one embodiment of a nuclear magnetic resonance spectrometer implantable device according to the invention. The static magnetic field is generated thanks to a permanent magnet arrangement.
It is to be noted that the static magnetic field must comply with two criteria.
Firstly the static magnetic field must be of high intensity. The intensity of the nuclear magnetic resonance signal is directly proportional to the number of atoms participating to the resonance, which is also directly proportional to the intensity of the magnetic field.
It is also possible to gather information related to the flow of a liquid by 2o analysing the signal returning to the equilibrium state after a resonant excitation.
This signal has a decrease, which is characteristic when the liquid is static, and a faster decrease when the liquid is in movement. This is due to the fact that part of the excited atoms will leave the detection volume of the antenna. This technique also used in magnetic resonance imaging spectroscopy devices.
Chronic monitoring of specific chemical compounds in a body fluid as well as gathering information relative to the flow rate of a fluid within the human body is a key in many areas of medicine, this is particularly true for brain metabolites monitoring in trauma patient or for monitoring the flow rate of the cerebrospinal fluid in a shunted hydrocephalic patient. The known techniques for monitoring the concentration of specific chemical compounds in a physiological fluid are usually achieved invasively either by techniques that require taking samples of the fluid (dialysis,..) or by inserting probes in the targeted fluid/tissue (micro dialysis, blood gas analysis.) These techniques involve either a puncture for each sample to analyse or a catheter line to be left in place for the duration of the monitoring.
Furthermore, invasive catheter probes are mainly targeted to specific analytes such as 02, C02, glucose or lactose.
Other non-invasive techniques such as magnetic resonance imaging spectroscopy are rather expensive and do not permit a continuous monitoring.
Moreover, concerning the flow rate assessment, there are currently no known devices to perform these measures in situ.
The aim of the present invention is to remedy the aforesaid drawbacks.
This goal is achieved by an implantable nuclear magnetic resonance spectrometer having the characteristic recited in claim 1.
Yet another object of the invention is the use of said implantable nuclear resonance spectrometer in several medical applications.
In accordance with one aspect, there is provided an implantable nuclear magnetic resonance spectrometer for at least one of measuring the chemical composition of a fluid and measuring the flow rate of the fluid, the spectrometer comprising: a housing; a catheter transversing across the housing so that a fluid external to the housing may flow through the catheter within the housing; a permanent magnet disposed within the housing that generates an intense homogenous magnetic field in the vicinity of the catheter; an electronics circuit disposed within the housing for detecting and formatting a nuclear magnetic resonance excitation signal; and at least one excitation coil connected to the electronic circuit and being disposed about the catheter to expose the fluid within the catheter to the excitation signal and to collect the nuclear magnetic resonance excitation signal.
In accordance with a further aspect, there is provided an apparatus for at least one of measuring the chemical composition of a physiological fluid and for measuring the flow rate of the fluid, comprising: an implantable nuclear magnetic 3a resonance spectrometer having a catheter extending therethrough so that a fluid external to the spectrometer may flow through the catheter to be analyzed; and an external reader having means for communicating with the implantable spectrometer by telemetry.
In accordance with a further aspect, there is provided use of the implantable nuclear magnetic resonance spectrometer described herein for at least one of measuring the chemical composition of a physiological fluid and measuring the flow rate of the fluid.
In accordance with a further aspect, there is provided use of the apparatus described herein for at least one of measuring the chemical composition of a physiological fluid and measuring the flow rate of the fluid.
Further features and other objects and advantages of this invention will become clear from the following detailed description made with reference to the accompanying drawings illustrating in a schematic and non-limiting way one embodiment of the implantable nuclear magnetic resonance spectrometer.
Figure 1 is a schematic partially cross-sectional view of the implantable nuclear magnetic resonance spectrometer object of the present invention.
Referring to fig 1, there is shown one embodiment of a nuclear magnetic resonance spectrometer implantable device according to the invention. The static magnetic field is generated thanks to a permanent magnet arrangement.
It is to be noted that the static magnetic field must comply with two criteria.
Firstly the static magnetic field must be of high intensity. The intensity of the nuclear magnetic resonance signal is directly proportional to the number of atoms participating to the resonance, which is also directly proportional to the intensity of the magnetic field.
Therefore, in order to generate a NMR signal that can be easily detected and analysed it is required to work with static magnetic field in the range of 1 Tesla and above. The second criterion that the magnetic field must fulfil is relative to its homogeneity. It is crucial that the sample to be analysed is immersed in whole in the same static magnetic field. If this is not the case, the de-excitation frequency spectrum will be broad ant thus difficult to measure and interpret. In the present case, the homogeneity of the static field should be in the range of 1-10 ppm.
A static magnetic field corresponding to these requirements is generated with an arrangement of permanent magnets. Back to figure 1, the arrangement of io permanent magnets is constituted of a cylindrical external permanent magnet 1.
The magnet arrangement comprises in addition two internal permanent magnets 2 also having a cylindrical shape. The magnets 1,2 are all polarised along their longitudinal axis. The direction of the magnetisation of both internal magnets 2 is identical but in the opposed direction of the polarisation of the external magnet 1.
(i.e, if the north pole of the external magnet 1 is located at the upper part of the external magnet 1, the internal magnets 2 will have their north pole toward the bottom of the figure). The magnet arrangement is completed with two magneto-concentrator 3 located on adjacent poles of the internal magnets 2. Their function is to improve the intensity and the homogeneity of the static magnetic field in the 2o region located directly in between the two internal magnets 2. Two ferrite caps 4 are closing this magnet arrangement and thus decreasing the loss of field appearing in that region.
The external magnet 1 is provided with two central radial holes 5 allowing the passage of a catheter 6 in between the two magneto-concentrators 3 ending the internal magnets 2. The fluid to analyse will flow in the catheter 6 in the center of the magnet arrangement. An excitation / detection coil 7 is arranged around the catheter 6 in the center of the permanent magnet structure. The volume of measure is determined by the volume of the coil which should be reduced in order to optimise the homogeneity of the field in the vicinity of the sample to analyse.
Simulations have shown that homogeneity of 1 ppm is obtained with a sphere having a diameter of a 100 m in the center of the structure for a field intensity of around 0,7 Tesla.
The excitation/detection coil 7 is connected to a electronic pre-pre-5 processing circuit 8 which, in a preferred embodiment, is located as close as possible to the coil 7 in order to increase the signal to noise ratio. This pre-processing circuit 8 which detects, amplify and pre-process the NMR signal is further connected to the main printed circuit board 9 which contains all the electronic components needed for the further processing of the signal. These io known components will not be described in details in the present specification but their main function can be summarised as follow. The main printed circuit board 9 comprises the necessary components to generate the nuclear magnetic resonance excitation signal at the resonance frequency. It further comprises the required components to format the signal detected by the pre-processing circuit 8.
The main circuit board 9 also includes the electronic components used for transferring the acquired and formatted data using state of the art telemetry.
To that extent a RF antenna 10 is located in the housing 11 of the implantable device.
When passive telemetry is used. the antenna 10 serves both for energising the printed circuit boards by inductive coupling and for transferring the formatted measured data to an external reader. An example of passive absorption modulation telemetry is disclosed in detail in the granted European patent No EP
0377695B1.
In an alternative embodiment, a power source like a battery can be incorporated in the housing 11 of the implantable device. This is the case when the energy needed exceeds the energy that can be transmitted by telemetry.
Active telemetry is widely used and known in the field of implantable medical devices. An apparatus and a method for telemetering both analog and digital data transcutaneously between an implantable medical device, like a pacemaker for example, and an external receiver or reader is described in US patent No 5,314,450 and can be implemented in order to transfer data bi-directionally between an external receiver (not shown) and the implantable device objet of the present invention.
The implantable device object of the invention will be encapsulated in a watertight housing in order to preserve the electronics components. The device may be for example completely encapsulated in a titanium housing which is bio-compatible and is therefore suitable for a long-term implantation in a human body.
Watertight passages will be provided in the housing at the level of the catheter 6 so that the fluid to analyse may flow through the catheter 6 for example by io diffusion.
Other isolation techniques may also be used, like the covering of the implantable device with bio-compatible polymers such as silicone or epoxy.
Thanks to the disclosed implantable device, it is possible to monitor continuously the composition and/or the concentration of specific chemical compounds in a physiological fluid. Once the device is implanted, it also allows the monitoring the fluid flow. One of the main advantage of this technique resides in the fact that it requires a one time implantation and then the implant can be interrogated non-invasively, by telemetry, whenever is needed and for as long time as needed. Many applications can be foreseen with this implantable device. By zo way of example, several use of the invention will be described.
Diabetic patients may need to test their blood glucose level several times a day. The proposed device objet of the invention may be implanted and then interrogated non-invasively by telemetry in order to perform an accurate monitoring of blood glucose level. This data will then be used to determine the optimal amount of insulin that needs to be injected. The implant could also be used to control automatically the injection rate of an implanted insulin infusion pump.
Other applications relates to the measurement of the effective flow rate out of an implanted drug delivery device as no implantable flow sensor are now available on the market. For example the knowledge of the effective flow rate in the shunt of a shunted hydrocephalic patient is a key for proper management of hydrocephalus. Implanting the proposed device along with the shunt would allow verifying that the shunt is working properly and allows optimisation of the settings of the shunt.
The implantable device may also be used for chronic monitoring of specific chemical compounds in a body fluid, in particular in trauma patients. Analytes that can be measured include metabolites such as amino acids, glucose, glutamate, lactose, dissolved gas, etc.
With such an implantable device, it is also possible to implement a feedback loop so that the implanted device may control other implantable devices like pacemaker or implanted drug delivery device depending on the results of the measured parameters.
A static magnetic field corresponding to these requirements is generated with an arrangement of permanent magnets. Back to figure 1, the arrangement of io permanent magnets is constituted of a cylindrical external permanent magnet 1.
The magnet arrangement comprises in addition two internal permanent magnets 2 also having a cylindrical shape. The magnets 1,2 are all polarised along their longitudinal axis. The direction of the magnetisation of both internal magnets 2 is identical but in the opposed direction of the polarisation of the external magnet 1.
(i.e, if the north pole of the external magnet 1 is located at the upper part of the external magnet 1, the internal magnets 2 will have their north pole toward the bottom of the figure). The magnet arrangement is completed with two magneto-concentrator 3 located on adjacent poles of the internal magnets 2. Their function is to improve the intensity and the homogeneity of the static magnetic field in the 2o region located directly in between the two internal magnets 2. Two ferrite caps 4 are closing this magnet arrangement and thus decreasing the loss of field appearing in that region.
The external magnet 1 is provided with two central radial holes 5 allowing the passage of a catheter 6 in between the two magneto-concentrators 3 ending the internal magnets 2. The fluid to analyse will flow in the catheter 6 in the center of the magnet arrangement. An excitation / detection coil 7 is arranged around the catheter 6 in the center of the permanent magnet structure. The volume of measure is determined by the volume of the coil which should be reduced in order to optimise the homogeneity of the field in the vicinity of the sample to analyse.
Simulations have shown that homogeneity of 1 ppm is obtained with a sphere having a diameter of a 100 m in the center of the structure for a field intensity of around 0,7 Tesla.
The excitation/detection coil 7 is connected to a electronic pre-pre-5 processing circuit 8 which, in a preferred embodiment, is located as close as possible to the coil 7 in order to increase the signal to noise ratio. This pre-processing circuit 8 which detects, amplify and pre-process the NMR signal is further connected to the main printed circuit board 9 which contains all the electronic components needed for the further processing of the signal. These io known components will not be described in details in the present specification but their main function can be summarised as follow. The main printed circuit board 9 comprises the necessary components to generate the nuclear magnetic resonance excitation signal at the resonance frequency. It further comprises the required components to format the signal detected by the pre-processing circuit 8.
The main circuit board 9 also includes the electronic components used for transferring the acquired and formatted data using state of the art telemetry.
To that extent a RF antenna 10 is located in the housing 11 of the implantable device.
When passive telemetry is used. the antenna 10 serves both for energising the printed circuit boards by inductive coupling and for transferring the formatted measured data to an external reader. An example of passive absorption modulation telemetry is disclosed in detail in the granted European patent No EP
0377695B1.
In an alternative embodiment, a power source like a battery can be incorporated in the housing 11 of the implantable device. This is the case when the energy needed exceeds the energy that can be transmitted by telemetry.
Active telemetry is widely used and known in the field of implantable medical devices. An apparatus and a method for telemetering both analog and digital data transcutaneously between an implantable medical device, like a pacemaker for example, and an external receiver or reader is described in US patent No 5,314,450 and can be implemented in order to transfer data bi-directionally between an external receiver (not shown) and the implantable device objet of the present invention.
The implantable device object of the invention will be encapsulated in a watertight housing in order to preserve the electronics components. The device may be for example completely encapsulated in a titanium housing which is bio-compatible and is therefore suitable for a long-term implantation in a human body.
Watertight passages will be provided in the housing at the level of the catheter 6 so that the fluid to analyse may flow through the catheter 6 for example by io diffusion.
Other isolation techniques may also be used, like the covering of the implantable device with bio-compatible polymers such as silicone or epoxy.
Thanks to the disclosed implantable device, it is possible to monitor continuously the composition and/or the concentration of specific chemical compounds in a physiological fluid. Once the device is implanted, it also allows the monitoring the fluid flow. One of the main advantage of this technique resides in the fact that it requires a one time implantation and then the implant can be interrogated non-invasively, by telemetry, whenever is needed and for as long time as needed. Many applications can be foreseen with this implantable device. By zo way of example, several use of the invention will be described.
Diabetic patients may need to test their blood glucose level several times a day. The proposed device objet of the invention may be implanted and then interrogated non-invasively by telemetry in order to perform an accurate monitoring of blood glucose level. This data will then be used to determine the optimal amount of insulin that needs to be injected. The implant could also be used to control automatically the injection rate of an implanted insulin infusion pump.
Other applications relates to the measurement of the effective flow rate out of an implanted drug delivery device as no implantable flow sensor are now available on the market. For example the knowledge of the effective flow rate in the shunt of a shunted hydrocephalic patient is a key for proper management of hydrocephalus. Implanting the proposed device along with the shunt would allow verifying that the shunt is working properly and allows optimisation of the settings of the shunt.
The implantable device may also be used for chronic monitoring of specific chemical compounds in a body fluid, in particular in trauma patients. Analytes that can be measured include metabolites such as amino acids, glucose, glutamate, lactose, dissolved gas, etc.
With such an implantable device, it is also possible to implement a feedback loop so that the implanted device may control other implantable devices like pacemaker or implanted drug delivery device depending on the results of the measured parameters.
Claims (10)
1. An implantable nuclear magnetic resonance spectrometer for at least one of measuring the chemical composition of a fluid and measuring the flow rate of the fluid, the spectrometer comprising: a housing; a catheter transversing across the housing so that a fluid external to the housing may flow through the catheter within the housing; a permanent magnet disposed within the housing that generates an intense homogenous magnetic field in the vicinity of the catheter; an electronics circuit disposed within the housing for detecting and formatting a nuclear magnetic resonance excitation signal; and at least one excitation coil connected to the electronic circuit and being disposed about the catheter to expose the fluid within the catheter to the excitation signal and to collect the nuclear magnetic resonance excitation signal.
2. An implantable nuclear magnetic resonance spectrometer according to claim 1, further comprising an antenna connected to the electric circuits for transmitting the formatted signal to an external reader unit by telemetry.
3. An implantable nuclear magnetic resonance spectrometer according to any one of claims 1 and 2, wherein the permanent magnet comprises an external cylindrical magnet and two internal cylindrical permanent magnets, each of the magnets having a polarization along its axis of symmetry, the direction of the polarization of the external magnet being in the opposed direction of the polarization of the two internal cylindrical permanent magnets.
4. An implantable nuclear magnetic resonance spectrometer according to claim 3, wherein the permanent magnet further comprises two ferrite caps closing the external cylindrical magnet and two magneto concentrators located at the adjacent extremity of the two internal cylindrical permanent magnets.
5. An implantable nuclear magnetic resonance spectrometer according to claim 4, wherein the excitation coil is disposed around the catheter traversing the two cylindrical internal permanent magnets, and a pre-processing circuit being disposed adjacent to the at least one excitation coil, the pre-processing circuit detecting and pre-processing the nuclear magnetic resonance signal.
6. An implantable nuclear magnetic resonance spectrometer according to any one of claims 1-5, further comprising a battery disposed within the housing for powering the electronic circuits.
7. An implantable nuclear magnetic resonance spectrometer according to any one of claims 1-6, wherein the housing is encapsulated in a bio-compatible material.
8. An apparatus for at least one of measuring the chemical composition of a physiological fluid and for measuring the flow rate of the fluid, comprising: an implantable nuclear magnetic resonance spectrometer having a catheter extending therethrough so that a fluid external to the spectrometer may flow through the catheter to be analyzed; and an external reader having means for communicating with the implantable spectrometer by telemetry.
9. Use of the implantable nuclear magnetic resonance spectrometer according to any one of claims 1-7 for at least one of measuring the chemical composition of a physiological fluid and measuring the flow rate of the fluid.
10. Use of the apparatus according to claim 8 for at least one of measuring the chemical composition of a physiological fluid and measuring the flow rate of the fluid.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00104778.6 | 2000-03-06 | ||
| EP00104778A EP1132048B1 (en) | 2000-03-06 | 2000-03-06 | Implantable nuclear magnetic resonance spectrometer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2339325A1 CA2339325A1 (en) | 2001-09-06 |
| CA2339325C true CA2339325C (en) | 2009-06-30 |
Family
ID=8168041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002339325A Expired - Fee Related CA2339325C (en) | 2000-03-06 | 2001-03-02 | Implantable nuclear magnetic resonance spectrometer |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6600945B2 (en) |
| EP (1) | EP1132048B1 (en) |
| JP (1) | JP4846112B2 (en) |
| AT (1) | ATE285709T1 (en) |
| CA (1) | CA2339325C (en) |
| DE (1) | DE60017074T2 (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9694166B2 (en) | 2002-03-26 | 2017-07-04 | Medtronics Ps Medical, Inc. | Method of draining cerebrospinal fluid |
| EP1534386A4 (en) * | 2002-06-04 | 2006-03-15 | Biophan Technologies Inc | Nuclear magnetic resonance spectrometer assembly |
| US6925322B2 (en) * | 2002-07-25 | 2005-08-02 | Biophan Technologies, Inc. | Optical MRI catheter system |
| US7781228B2 (en) * | 2005-04-07 | 2010-08-24 | Menon & Associates, Inc. | Magnetic resonance system and method to detect and confirm analytes |
| EP1932009B1 (en) | 2005-08-31 | 2014-02-12 | T2 Biosystems, Inc. | Nmr device for detection of analytes involving magnetic particles |
| AU2007317787B2 (en) | 2006-11-08 | 2012-07-12 | T2 Biosystems, Inc. | NMR systems for in vivo detection of analytes |
| WO2009082286A1 (en) * | 2007-12-21 | 2009-07-02 | St. Jude Medical Ab | Implantable analyte rf spectroscopy measuring system |
| US20120223705A1 (en) * | 2007-12-21 | 2012-09-06 | T2 Biosystems, Inc. | Magnetic resonance system with implantable components and methods of use thereof |
| DE102010020152B4 (en) | 2010-05-11 | 2013-10-24 | Siemens Aktiengesellschaft | Device with local coil arrangement and implantable device |
| US8729893B2 (en) * | 2010-10-19 | 2014-05-20 | Baker Hughes Incorporated | Nuclear magnetic resonance 1H and 13C multiphase flow measurements, estimating phase selected flow rates from velocity distributions, volume fractions, and mean velocity |
| US20120197107A1 (en) * | 2011-01-31 | 2012-08-02 | Case Western Reserve University | Glucose analyzing blood examiner (gabe) |
| US20140194715A1 (en) * | 2011-01-31 | 2014-07-10 | Case Western Reserve University | Glucose Analyzing Blood Examiner |
| KR20150016214A (en) | 2012-03-16 | 2015-02-11 | 바이탈 센서즈 홀딩 컴퍼니 인코포레이티드 | Permittivity shielding |
| DE102018222446A1 (en) * | 2018-12-20 | 2020-06-25 | Robert Bosch Gmbh | NMR measuring device and use of the NMR measuring device |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5072732A (en) * | 1986-09-04 | 1991-12-17 | Advanced Techtronics, Inc. | NMR instrument for testing for fluid constituents |
| US5035231A (en) * | 1987-04-27 | 1991-07-30 | Olympus Optical Co., Ltd. | Endoscope apparatus |
| JPH01299544A (en) * | 1988-05-27 | 1989-12-04 | Hitachi Ltd | Mri photographing method |
| CH676164A5 (en) | 1988-05-28 | 1990-12-14 | Sc Techn Dipl Ing Peter A Neuk | |
| US5127404A (en) | 1990-01-22 | 1992-07-07 | Medtronic, Inc. | Telemetry format for implanted medical device |
| JPH067322A (en) * | 1992-06-29 | 1994-01-18 | Olympus Optical Co Ltd | Mr endoscope device |
| US5572132A (en) * | 1995-08-15 | 1996-11-05 | Pulyer; Yuly M. | MRI probe for external imaging |
| JPH1057339A (en) * | 1996-08-19 | 1998-03-03 | Ge Yokogawa Medical Syst Ltd | Measuring mr signal, apparatus therefor and mr probe |
| DE19746735C2 (en) * | 1997-10-13 | 2003-11-06 | Simag Gmbh Systeme Und Instr F | NMR imaging method for the display, position determination or functional control of a device inserted into an examination object and device for use in such a method |
| CA2391523C (en) * | 1999-11-16 | 2012-08-21 | Ernest Wollin | Magnetic resonance analyzing flow meter and flow measuring method |
| EP1132047B1 (en) * | 2000-03-06 | 2004-12-29 | Medos SA | Mini-invasive nuclear magnetic resonance spectroscopy catheter probe |
-
2000
- 2000-03-06 AT AT00104778T patent/ATE285709T1/en active
- 2000-03-06 EP EP00104778A patent/EP1132048B1/en not_active Expired - Lifetime
- 2000-03-06 DE DE60017074T patent/DE60017074T2/en not_active Expired - Lifetime
-
2001
- 2001-03-02 US US09/797,818 patent/US6600945B2/en not_active Expired - Fee Related
- 2001-03-02 CA CA002339325A patent/CA2339325C/en not_active Expired - Fee Related
- 2001-03-05 JP JP2001060801A patent/JP4846112B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60017074D1 (en) | 2005-02-03 |
| US20010029331A1 (en) | 2001-10-11 |
| DE60017074T2 (en) | 2006-03-30 |
| JP4846112B2 (en) | 2011-12-28 |
| EP1132048B1 (en) | 2004-12-29 |
| ATE285709T1 (en) | 2005-01-15 |
| US6600945B2 (en) | 2003-07-29 |
| JP2001269326A (en) | 2001-10-02 |
| EP1132048A1 (en) | 2001-09-12 |
| CA2339325A1 (en) | 2001-09-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8836334B2 (en) | NMR systems for in vivo detection of analytes | |
| CA2339325C (en) | Implantable nuclear magnetic resonance spectrometer | |
| US4875486A (en) | Instrument and method for non-invasive in vivo testing for body fluid constituents | |
| US5072732A (en) | NMR instrument for testing for fluid constituents | |
| EP2905631A1 (en) | Magnetic resonance system with implantable components and methods of use thereof | |
| US20070035296A1 (en) | Method for measuring nuclear magnetic resonance longitudinal axis relaxation time of blood and apparatus using the same | |
| US8570035B2 (en) | Magnetic resonance imaging of living systems by remote detection | |
| Vassiliou et al. | Miniaturized, biopsy-implantable chemical sensor with wireless, magnetic resonance readout | |
| CA2339316C (en) | Mini-invasive nuclear magnetic resonance spectroscopy catheter probe | |
| US5879300A (en) | Magnetic resonance methods and apparatus | |
| CA1288475C (en) | Instrument and method for testing for fluid constituents | |
| Balaban | NMR spectroscopy of the heart, part I | |
| KR20050107138A (en) | Instrument and method for non-invasive in vivo testing for body fluid constituents using nmr | |
| US20080139927A1 (en) | Implantable Chamber, Imaging Method and Magnetic Resonance Imaging System | |
| Vassiliou | Biopsy-implantable chemical sensor | |
| WO2020127028A1 (en) | Nmr measuring apparatus having a sensor device for intracorporeal arrangement |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160302 |